Module 3 - Strategic case studies in practice

Pharmaceutical Development

knowledge gained, and not the volume of data, provides the basis for science-based submissions and their regulatory evaluation.

2.1

Components of the Drug Product

2.1.1 Drug Substance The physicochemical and biological properties of the drug substance that can influence the performance of the drug product and its manufacturability, or were specifically designed into the drug substance (e.g., solid state properties), should be identified and discussed. Examples of physicochemical and biological properties that might need to be examined include solubility, water content, particle size, crystal properties, biological activity, and permeability. These properties could be inter- related and might need to be considered in combination. To evaluate the potential effect of drug substance physicochemical properties on the performance of the drug product, studies on drug product might be warranted. For example, the ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances describes some of the circumstances in which drug product studies are recommended (e.g., Decision Tree #3 and #4 (Part 2)). This approach applies equally for the ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnology/Biological Products . The knowledge gained from the studies investigating the potential effect of drug substance properties on drug product performance can be used, as appropriate, to justify elements of the drug substance specification (3.2.S.4.5). The compatibility of the drug substance with excipients listed in 3.2.P.1 should be evaluated. For products that contain more than one drug substance, the compatibility of the drug substances with each other should also be evaluated. 2.1.2 Excipients The excipients chosen, their concentration, and the characteristics that can influence the drug product performance (e.g., stability, bioavailability) or manufacturability should be discussed relative to the respective function of each excipient. This should include all substances used in the manufacture of the drug product, whether they appear in the finished product or not (e.g., processing aids). Compatibility of excipients with other excipients, where relevant (for example, combination of preservatives in a dual preservative system), should be established. The ability of excipients (e.g., antioxidants, penetration enhancers, disintegrants, release controlling agents) to provide their intended functionality, and to perform throughout the intended drug product shelf life, should also be demonstrated. The information on excipient performance can be used, as appropriate, to justify the choice and quality attributes of the excipient, and to support the justification of the drug product specification (3.2.P.5.6). Information to support the safety of excipients, when appropriate, should be cross- referenced (3.2.P.4.6).

2.2

Drug Product

2.2.1 Formulation Development A summary should be provided describing the development of the formulation, including identification of those attributes that are critical to the quality of the drug

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